Although autism has historically been conceptualized as a condition that emerges in early childhood1,2, many autistic people are diagnosed later in life3, 4–5. It is unknown whether earlier- and later-diagnosed autism have different developmental trajectories and genetic profiles. Using longitudinal data from four independent birth cohorts, we demonstrate that two different socioemotional and behavioural trajectories are associated with age at diagnosis. In independent cohorts of autistic individuals, common genetic variants account for approximately 11% of the variance in age at autism diagnosis, similar to the contribution of individual sociodemographic and clinical factors, which typically explain less than 15% of this variance. We further demonstrate that the polygenic architecture of autism can be broken down into two modestly genetically correlated (rg = 0.38, s.e. = 0.07) autism polygenic factors. One of these factors is associated with earlier autism diagnosis and lower social and communication abilities in early childhood, but is only moderately genetically correlated with attention deficit–hyperactivity disorder (ADHD) and mental-health conditions. Conversely, the second factor is associated with later autism diagnosis and increased socioemotional and behavioural difficulties in adolescence, and has moderate to high positive genetic correlations with ADHD and mental-health conditions. These findings indicate that earlier- and later-diagnosed autism have different developmental trajectories and genetic profiles. Our findings have important implications for how we conceptualize autism and provide a model to explain some of the diversity found in autism. A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Patients with post-traumatic stress disorder face increased cardiovascular risk. This study examines shared genetic regions between post-traumatic stress disorder and 246 cardiovascular conditions across electronic health records, 82 cardiac imaging, and health behaviors defined by Life’s Essential 8. Post-traumatic stress disorder is genetically correlated with cardiovascular diagnoses in 33 regions, imaging traits in 4 regions, and health behaviors in 44 regions. Potentially shared causal variants between post-traumatic stress disorder and 17 cardiovascular conditions were observed in 11 regions. Subsequent observational analysis in AllofUS cohort showed post-traumatic stress disorder is associated with 13 diagnoses even after accounting for socioeconomic factors and depression. Genetically regulated proteome expression in brain and blood tissues identified 33 blood and 122 brain genes shared between the two conditions, revealing neuronal, immune, metabolic, and calcium-related mechanisms, with several genes as targets for existing drugs. These findings exhibit shared risk loci and genes are involved in tissue-specific mechanisms. Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

Introduction Posttraumatic stress disorder in the paediatric population has clinical features. The Clinician-Administered PTSD Scale for DSM-5,child and adolescent version (CAPS-CA-5) is the gold standard for the positive diagnosis. Objectives The objectives of our work were to translate the CAPS-CA-5 into Tunisian dialectal Arabic and to validate it in our Tunisian sociocultural context. Methods This is a descriptive cross-sectional study conducted in the child psychiatry department of Mongi Slim Hospital and the forensic medicine department of Charles-Nicolle Hospital (Tunisia), among children older than seven years who were exposed to a potentially traumatic event at least one month before. We validated the tool through translation, content, construct validity and reliability. The statistical processing for this data was carried out using SPSS 26 software. Results We conducted our study with 150 patients. The validation was made on 146 records after the exclusion of 4 incompleted assessments. We initially translated the CAPS-CA-5 into Tunisian dialect. We validated the content through pre-test and scientific committee evaluation. Afterwards, we validated the construction. We calculated the Bartlett’s sphericity test (p<0.001) .The KMO index that was 0.766. Concerning the reliability study, we found a Cronbach’s alpha coefficient equal to 0.92. We studied also the inter-raters reliability; we found an intra-class coefficient between 0.8 and 1 Conclusions We validated the first Tunisian diagnostic tool for PTSD in children according to the DSM-5 criteria with satisfactory psychometric qualities. Disclosure of Interest None Declared

Background: Globally, life expectancy is increasing, leading to an equal proportion of elderly and young individuals, which carries extensive implications. In Bosnia and Herzegovina (BiH), the average age at death in 2021 was 77 years, positioning BiH in the middle of the global list of average life expectancy. Current studiesinvestigate whether the prevalence of psychiatric disorders increases or decreases with age, but results are inconsistent regarding the role of age.There is no prior research on mental disorders in the elderly population in BiH. The experience of the previous war in BiH and the post-war complex “transitional period” have been associated with specific challenges to the mental health of this population, inspiring our research topic. Objective: The aim of this study was to investigate the psychiatric morbidity in hospitalized individuals aged≥55 years. Methods: The sample consisted of all patients over age 55 treated at the Department of Psychiatry in Tuzla between January 2018 and December 2020 (N=637), divided into four age categories. Data were obtained from medical records, and for research purposes, a specific questionnaire was constructed. Results: The predominant psychiatric morbidity stemmed from the category of affective disorders, most common within the “55-64 years” age group, while organic mental disorders were more prevalent in other age groups.Substance use disorders were present in patients aged “55-64 years”, with a sharp decline in their prevalence in older age. Female participants had a significantly higher prevalence of affective, psychotic, neurotic, and stress-related disorders, whereas male participants exhibited an increased prevalence of organic mental and substance use disorders. Conclusion: In total sample, the most prevalent diagnoses belong to the category of affective disorders. Female were most frequently diagnosed with affective disorders, whereas organic mental disorders and substance use disorders prevail in male.

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24–71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10−8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q < 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further.

Posttraumatic stress disorder (PTSD) is triggered by extremely stressful environmental events and characterized by high emotional distress, re-experiencing of trauma, avoidance and hypervigilance. The present study uses polygenic risk scores (PRS) derived from the UK Biobank (UKBB) mega-cohort analysis as part of the PGC PTSD GWAS effort to determine the heritable basis of PTSD in the South Eastern Europe (SEE)-PTSD cohort. We further analyzed the relation between PRS and additional disease-related variables, such as number and intensity of life events, coping, sex and age at war on PTSD and CAPS as outcome variables. Association of PRS, number and intensity of life events, coping, sex and age on PTSD were calculated using logistic regression in a total of 321 subjects with current and remitted PTSD and 337 controls previously subjected to traumatic events but not having PTSD. In addition, PRS and other disease-related variables were tested for association with PTSD symptom severity, measured by the Clinician Administrated PTSD Scale (CAPS) by liner regression. To assess the relationship between the main outcomes PTSD diagnosis and symptom severity, each of the examined variables was adjusted for all other PTSD related variables. The categorical analysis showed significant polygenic risk in patients with remitted PTSD and the total sample, whereas no effects were found on symptom severity. Intensity of life events as well as the individual coping style were significantly associated with PTSD diagnosis in both current and remitted cases. The dimensional analyses showed as association of war-related frequency of trauma with symptom severity, whereas the intensity of trauma yielded significant results independently of trauma timing in current PTSD. The present PRS application in the SEE-PTSD cohort confirms modest but significant polygenic risk for PTSD diagnosis. Environmental factors, mainly the intensity of traumatic life events and negative coping strategies, yielded associations with PTSD both categorically and dimensionally with more significant p-values. This suggests that, at least in the present cohort of war-related trauma, the association of environmental factors and current individual coping strategies with PTSD psychopathology was stronger than the polygenic risk.